Successful hematogenous metastasis of tumor cells requires specific interactions with vascular endothelial cells, as tumor cells enter the circulation and as they invade through blood vessels into extravascular tissues. These interactions have proven difficult to study in vivo and little is known concerning the molecular mechanisms of these interactions. Therefore, it is the objective of this proposal to use an established line of adult bovine aortic endothelial cells to study in vitro tumor-endothelial cell interactions. The tumor cell lines to be used in these studies have been selected for increased metastasis by in vivo selection procedures, and in this way high- and low-metastatic tumor cell lines can be compared directly for differences in interaction with endothelial cells. The following specific areas of study will be considered: 1) the mitogenic effects of tumor cells on endothelial cells; 2) the ability of tumor cells to degrade monolayers of endothelial cells and extracellular matrix, which is deposited underneath the monolayer and is similar to a basement membrane in vivo. The possible role of plasminogen activator in degradation will be examined; 3) morphological and ultrastructural studies of tumor-endothelial cell interaction by light, scanning electron and transmission electron microscopy; 4) the role of fibronectin in tumor-endothelial cell interactions. Fibronectin has recently been shown to be a major component of endothelial cell basement membrane and may be involved in the adhesion of endothelial cells to their basement membrane.